Renal Denervation and Salt Induced Hypertension

A high-salt diet is linked to elevation in blood pressure in salt sensitive individuals. The relationship between chronic high dietary salt intake and blood pressure variability has been established in many experimental studies, especially in primary hypertensive patients. Nonetheless, the exact mechanism underlying this relationship remains unclear. Functional disturbance in the kidney is considered to be an important factor in mediating the effect of high salt on arterial blood pressure. High salt ingestion over long periods of time alters kidney function through its effect on renal hemodynamic and tubular function that subsequently decreases renal salt and fluid excretory capacity. This could greatly affect the body fluid homeostasis leading to a high blood pressure response. On another hand, high sodium induced blood pressure response in the kidney is associated with increased urinary albumin excretion possibly due to salt induced blood pressure effect on glomerular arteriole causing endothelial cell damage. Furthermore, recent reports suggest that high salt induced damage of ultrafiltration barrier and proteinuria is due to a decrease in nephron, a protein found in glomerular capillary bed and an increase in angiotensin converting enzyme/angiotensin converting enzyme 2 (ACE/ACE2) ratios. However, it is also reported that the resultant state of renal impairment in response to high salt intake can occur independently of any variations in blood pressure. Hence, the adverse effects of high salt intake on renal function involve various underlying mechanisms.

Elevated renal sympathetic nerve activity has been suggested as a key factor in mediating salt related renal impairment. The role of the renal sympathetic nerves in the development of salt induced hypertension is supported by pharmacological and renal denervation studies. The renal sympathetic nervous system directly innervates all the components of the kidney including the tubules, vessels, and juxtaglomerular apparatus. Through this pattern of innervation, the renal sympathetic nerves regulate renal hemodynamic and tubular functions. Tubular effects of renal nerve stimulation include a decrease in urinary sodium and water excretion while renal hemodynamic responses include a decrease in renal blood flow, and glomerular filtration. Additionally, renal nerve input increases the release of angiotensin II (Ang II) from the juxtaglomerular apparatus. The renal effects of Ang II include renal tubular salt and water reabsorption, arteriolar constriction and decreased renal blood flow. Consequently, elevated renal nerve activity in salt induced hypertensive conditions will influence these abovementioned renal hemodynamic and tubular functions, which will have a greater impact on arterial blood pressure.

The salt-induced alteration of the sympathetic system and its impact on renal function and hemodynamic were found to be mediated through various adrenoreceptors. Studies have reported that the density and sensitivity of adrenoceptors in the renal vasculature are altered in hypertensive and normotensive subjects in conditions of high salt load. This observation is supported by elevated renal vascular responses to administered adrenergic agonist. Further, it is reported that high salt intake enhances the sensitivity of specific subtypes of adrenoceptor. Among the various subtypes of renal adrenoceptors, α1A-subtype was found to play a major role in renal cortical vascular hypersensitivity, antidiuretic, and antinatriuresis in spontaneously hypertensive rats under conditions of high salt diet. Additionally, findings from a study in Westar rats subjected to a high-salt diet implicated the functional involvement of α1B-adrenoceptors in mediating the effects of high salt on the renal vasculature. On another hand, increased α2B-adrenoreceptor gene expression, density and protein expression were also observed in association with salt-induced elevations in blood pressure in sabra hypertension prone rats. Therefore, it seems that various subtypes of adrenoceptors are involved in mediating salt-induced effects on renal function.Journal of Nephrology and Urology is an Open Access peer-reviewed publication that discusses current research and advancements in diagnosis and management of kidney disorders as well as related epidemiology, pathophysiology and molecular genetics.

To submit a new manuscript authors should use the online submission system. Authors may submit their manuscript via online tracking system https://www.imedpub.com/submissions/nephrology-urology.html or as an attachment to email:  nephrolurol@imedpubjournals.com

Regards
Mercy Eleanor
Editorial Assistant
Journal of Nephrology and Urology